Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients

A pilot study

Giorgio Aquila, Cinzia Fortini, Antonio Pannuti, Serena Delbue, Micaela Pannella, Marco Bruno Morelli, Cristiana Caliceti, Fausto Castriota, Monica Mattei, Alessia Ongaro, Agnese Pellati, Pasquale Ferrante, Lucio Miele, Luigi Tavazzi, Roberto Ferrari, Paola Rizzo, Alberto Cremonesi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p,146-5p, 155-5p, 424-5p. We found an "inflamed plaque" gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a "stable plaque" profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics. Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.

Original languageEnglish (US)
Article number98
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
StatePublished - May 4 2017
Externally publishedYes

Fingerprint

Peripheral Arterial Disease
Transcriptome
Gene expression
Vascular Cell Adhesion Molecule-1
Cyclooxygenase 2
Muscle
Smooth Muscle
Genes
Femoral Artery
Polymerase chain reaction
RNA-Directed DNA Polymerase
MicroRNAs
Atherectomy
Popliteal Artery
Chemical activation
RNA
Thigh
Ligands
Reverse Transcriptase Polymerase Chain Reaction
Disease Progression

Keywords

  • Inflammation
  • Macrophages
  • MicroRNA
  • Notch
  • Peripheral artery disease
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients : A pilot study. / Aquila, Giorgio; Fortini, Cinzia; Pannuti, Antonio; Delbue, Serena; Pannella, Micaela; Morelli, Marco Bruno; Caliceti, Cristiana; Castriota, Fausto; Mattei, Monica; Ongaro, Alessia; Pellati, Agnese; Ferrante, Pasquale; Miele, Lucio; Tavazzi, Luigi; Ferrari, Roberto; Rizzo, Paola; Cremonesi, Alberto.

In: Journal of Translational Medicine, Vol. 15, No. 1, 98, 04.05.2017.

Research output: Contribution to journalArticle

Aquila, G, Fortini, C, Pannuti, A, Delbue, S, Pannella, M, Morelli, MB, Caliceti, C, Castriota, F, Mattei, M, Ongaro, A, Pellati, A, Ferrante, P, Miele, L, Tavazzi, L, Ferrari, R, Rizzo, P & Cremonesi, A 2017, 'Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients: A pilot study', Journal of Translational Medicine, vol. 15, no. 1, 98. https://doi.org/10.1186/s12967-017-1199-3
Aquila, Giorgio ; Fortini, Cinzia ; Pannuti, Antonio ; Delbue, Serena ; Pannella, Micaela ; Morelli, Marco Bruno ; Caliceti, Cristiana ; Castriota, Fausto ; Mattei, Monica ; Ongaro, Alessia ; Pellati, Agnese ; Ferrante, Pasquale ; Miele, Lucio ; Tavazzi, Luigi ; Ferrari, Roberto ; Rizzo, Paola ; Cremonesi, Alberto. / Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients : A pilot study. In: Journal of Translational Medicine. 2017 ; Vol. 15, No. 1.
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abstract = "Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p,146-5p, 155-5p, 424-5p. We found an {"}inflamed plaque{"} gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a {"}stable plaque{"} profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics. Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.",
keywords = "Inflammation, Macrophages, MicroRNA, Notch, Peripheral artery disease, Vascular smooth muscle cells",
author = "Giorgio Aquila and Cinzia Fortini and Antonio Pannuti and Serena Delbue and Micaela Pannella and Morelli, {Marco Bruno} and Cristiana Caliceti and Fausto Castriota and Monica Mattei and Alessia Ongaro and Agnese Pellati and Pasquale Ferrante and Lucio Miele and Luigi Tavazzi and Roberto Ferrari and Paola Rizzo and Alberto Cremonesi",
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T1 - Distinct gene expression profiles associated with Notch ligands Delta-like 4 and Jagged1 in plaque material from peripheral artery disease patients

T2 - A pilot study

AU - Aquila, Giorgio

AU - Fortini, Cinzia

AU - Pannuti, Antonio

AU - Delbue, Serena

AU - Pannella, Micaela

AU - Morelli, Marco Bruno

AU - Caliceti, Cristiana

AU - Castriota, Fausto

AU - Mattei, Monica

AU - Ongaro, Alessia

AU - Pellati, Agnese

AU - Ferrante, Pasquale

AU - Miele, Lucio

AU - Tavazzi, Luigi

AU - Ferrari, Roberto

AU - Rizzo, Paola

AU - Cremonesi, Alberto

PY - 2017/5/4

Y1 - 2017/5/4

N2 - Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p,146-5p, 155-5p, 424-5p. We found an "inflamed plaque" gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a "stable plaque" profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics. Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.

AB - Background: The lack of early diagnosis, progression markers and effective pharmacological treatment has dramatic unfavourable effects on clinical outcomes in patients with peripheral artery disease (PAD). Addressing these issues will require dissecting the molecular mechanisms underlying this disease. We sought to characterize the Notch signaling and atherosclerosis relevant markers in lesions from femoral arteries of symptomatic PAD patients. Methods: Plaque material from the common femoral, superficial femoral or popliteal arteries of 20 patients was removed by directional atherectomy. RNA was obtained from 9 out of 20 samples and analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: We detected expression of Notch ligands Delta-like 4 (Dll4) and Jagged1 (Jag1), of Notch target genes Hes1, Hey1, Hey2, HeyL and of markers of plaque inflammation and stability such as vascular cell adhesion molecule 1 (VCAM1), smooth muscle 22 (SM22), cyclooxygenase 2 (COX2), Bcl2, CD68 and miRNAs 21-5p, 125a-5p, 126-5p,146-5p, 155-5p, 424-5p. We found an "inflamed plaque" gene expression profile characterized by high Dll4 associated to medium/high CD68, COX2, VCAM1, Hes1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p and low Jag1, SM22, Bcl2, Hey2, HeyL, miR125a-5p (2/9 patients) and a "stable plaque" profile characterized by high Jag1 associated to medium/high Hey2, HeyL, SM22, Bcl2, miR125a and low Dll4, CD68, COX2, VCAM1, miR126-5p, miR146a-5p, miR155-5p, miR424-5p (3/9 patients). The remaining patients (4/9) showed a plaque profile with intermediate characteristics. Conclusions: This study reveals the existence of a gene signature associated to Notch activation by specific ligands that could be predictive of PAD progression.

KW - Inflammation

KW - Macrophages

KW - MicroRNA

KW - Notch

KW - Peripheral artery disease

KW - Vascular smooth muscle cells

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